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Vibrations are an issue of increasing importance in current footbridge design practice. More sophisticated footbridges with increasing spans and more effective construction materials result in lightweight structures and a high ratio of live load to dead load. As a result of this trend, many footbridges have become more susceptible to vibrations when subjected to dynamic loads. The most common dynamic loads on footbridges, other than wind loading, are pedestrian-induced footfall forces due to the movement of people. This paper concerns the experimental and numerical dynamic characterization of a newly built steel and wooden cable-stayed footbridge. The footbridge was dynamically tested in situ under ambient vibration, and the results allowed the real dynamic behavior of the footbridge to be captured. The dynamic response under pedestrian dynamic loads was also investigated and compared with the limitations provided by the main international codes and guidelines for footbridge serviceability assessment. A numerical model of the footbridge was also developed and updated based on the experimental outcomes. Then, the calibrated model was used to numerically assess the footbridge's serviceability following the guideline prescriptions for pedestrian load simulation, and the design accuracy was also validated. This paper aims to increase the state-of-the-art knowledge about footbridge dynamic testing so as to support the design of new and futuristic structures as well as prove the effectiveness of using the requirements of codes and guidelines for footbridge serviceability assessment by adopting a calibrated numerical model. [ABSTRACT FROM AUTHOR]

Many transportation infrastructures all around the world are facing new challenges in terms of ageing and loss of performance. The infrastructural asset managers are required to perform scrupulous control of the health condition of the infrastructures over time and to execute the required maintenance works. In this context, digital twin models of the infrastructures should have a key role to simplify and speed up the procedures for proper maintenance. This paper discusses the advantages of developing digital twin models for the management of infrastructures, with a focus on bridges. In particular, the role of dynamic tests performed on bridges for the development of digital twin models is addressed, paying attention to test procedures and requirements. Issues such as the quality of instrumentation, the numerosity, and layout of sensors, and the acquisition and post-processing procedures are addressed through applications to two real bridge case studies. Both infrastructures are multi-span pre-stressed RC bridges that were dynamically tested after the restoration and seismic upgrading works. Results of ambient vibration tests and operational modal analyses are described, providing an idea of dynamic test requirements, as well as their use within the framework of the digital twin model creation. [ABSTRACT FROM AUTHOR]

DNA gyrase is an important target for the development of novel antibiotics. Although ATP-competitive DNA gyrase (GyrB) inhibitors are a well-studied class of antibacterial agents, there is currently no representative used in therapy, largely due to unwanted off-target activities. Selectivity of GyrB inhibitors against closely related human ATP-binding enzymes should be evaluated early in development to avoid off-target binding to homologous binding domains. To address this challenge, we developed selective 3D-pharmacophore models for GyrB, human topoisomerase IIα (TopoII), and the Hsp90 N-terminal domain (NTD) to be used in in silico activity profiling paradigms to identify molecules selective for GyrB over TopoII and Hsp90, as starting points for hit expansion and lead optimization. The models were used to profile highly active GyrB, TopoII, and Hsp90 inhibitors. Selected compounds were tested in in vitro assays. GyrB inhibitors 1 and 2 were inactive against TopoII and Hsp90, while 3 and 4, potent Hsp90 inhibitors, displayed no inhibition of GyrB and TopoII, and TopoII inhibitors 5 and 6 were inactive at GyrB and Hsp90. The results provide a proof of concept for the use of target activity profiling methods to identify selective starting points for hit and lead identification. [ABSTRACT FROM AUTHOR]